Surgical slings

ABSTRACT

The invention relates generally to surgical implants, and in various embodiments to surgical implants configured for promoting growth of well-organized collagenous tissue at an anatomical site.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.60/495,439, filed Aug. 14, 2003, the entire disclosure of which isincorporated herein by reference.

TECHNICAL FIELD

The invention generally relates to surgical slings and related methods.More particularly, in one embodiment, the invention relates to surgicalslings, such as midurethral slings, that promote growth of collagenoustissue, such as scar tissue, in a well-organized manner.

BACKGROUND INFORMATION

Urinary incontinence affects over 13 million men and women of all agesin the United States. Stress urinary incontinence (SUI) affectsprimarily women and is generally caused by two conditions, intrinsicsphincter deficiency (ISD) and hypermobility. These conditions may occurindependently or in combination. In ISD, the urinary sphincter valve,located within the urethra, fails to close properly (coapt), causingurine to leak out of the urethra during stressful activity.Hypermobility is a condition in which the pelvic floor is distended,weakened, or damaged, causing the bladder neck and proximal urethra torotate and descend in response to increases in intra-abdominal pressure(e.g., due to sneezing, coughing, straining, etc.). The result is thatthere is an insufficient response time to promote urethral closure and,consequently, urine leakage and/or flow results. A popular treatment ofSUI is the use of a sling, which is permanently placed under a patient'sbladder neck or mid-urethra to provide a urethral platform. Placement ofthe sling limits the endopelvic fascia drop, while providing compressionto the urethral sphincter to improve coaptation.

However, permanently placing the sling in a patient's periurethraltissues may cause complications necessitating further surgicalintervention. For instance, changes in a patient's body weight and/oranatomy over the course of his/her life, may cause the sling to contactthe patient's urethra, an undesirable side effect that may result indiscomfort and more serious medical problems such as urethral erosionfor the patient. As further examples, a patient with a sling permanentlyplaced in her periurethral tissues may suffer vaginal mucosal erosion ofthe vaginal incision and/or permanent urinary retention. Thesecomplications also require further surgical intervention to resect thesling.

Due to deficiencies in the prior art, improved surgically implantableslings are needed.

SUMMARY OF THE INVENTION

The invention provides, in one embodiment, a surgically implantablesling (hereinafter a “surgical sling”) that includes a pharmaceuticalagent (e.g., an agent or other therapeutic treatment) or mixture ofpharmaceutical agents (hereinafter collectively an “agent”). Accordingto one feature, the surgical sling is, at least in part, biodegradable,while the agent, by stimulating the patient's periurethral tissues,promotes collagenous tissue growth, such as scar tissue, in awell-organized manner surrounding the implanted sling. According to oneaspect, when first placed in the patient's periurethral tissues, thebiodegradable sling provides physical support to the patient's urethra.As the biodegradable sling degrades and gradually disappears over time,the patient's tissues form a sling, which includes collagenous tissue,such as scar tissue, formed as a result of stimulating the patient'slocal tissues with the agent. This endogenous/natural collagenous tissuesling provides the requisite support to assist in the correction of thepatient anatomy of the local tissues and therefore maintainingcontinence. According to one feature, the invention reduces the need fora permanent sling, of the type provided by the prior art, byfacilitating formation of the natural tissue sling.

In one aspect, the invention provides a surgical sling for treatingurinary incontinence in a patient. The surgical sling includes aplurality of biocompatible fibers and an agent associated with a subsetof the fibers. According to one feature, the agent promotes collagenoustissue growth, such as scar tissue, in a well-organized manneroriginating from the patient's tissues at the location of implantation.

In one configuration, a subset of the plurality of biocompatible fibersof the sling is biodegradable. According to another configuration, theagent includes a growth factor and a hormone, such as estrogen, forfacilitating collagenous tissue growth, such as scar tissue. The agentmay be, for example, chemically bonded to a subset of the biocompatiblefibers, applied as a coating to a subset of the biocompatible fibers,and/or absorbed within the biocompatible fibers. Alternatively, a subsetof the plurality of biocompatible fibers may be a blend of the agent anda polymer. The agent may be impregnated into the biocompatible fibers.In another configuration, a subset of the plurality of the biocompatiblefibers define a plurality of openings in the surgical sling and ahydrogel containing the agent is applied to the plurality of openings inthe sling. In other configurations, the agent may be associated with asubset of the biocompatible fibers and/or the surgical sling as a wholein any suitable manner.

According to another embodiment, the surgical sling includes a pluralityof biocompatible and biodegradable fibers with certain surfaceproperties that promote host tissue/cell attachment and further attractand/or promote host tissue growth. In one configuration, the surgicalsling includes a plurality of surface properties such as channels toguide the growth of the collagenous tissue such as scar tissue at ananatomical implantation site in the body of the patient. Alternatively,the surgical sling may include one or more through holes for guiding thegrowth of the collagenous tissue.

In another aspect, the invention provides methods for treating urinaryincontinence with a surgical sling according to the invention.

The foregoing and other objects, aspects, features, and advantages ofthe invention will be apparent from the following illustrativedescription.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, like reference characters generally refer to the sameparts throughout the different views. Also, the drawings are notnecessarily to scale, emphasis instead generally being placed uponillustrating principles of the invention.

FIG. 1 is a view of a surgical sling according to an illustrativeembodiment of the invention.

FIG. 2 is a view of a surgical sling according to another illustrativeembodiment of the invention.

FIG. 3 is a view of a surgical sling according to another illustrativeembodiment of the invention, showing a weave made of more than one typeof material.

FIG. 4 is a view of a surgical sling according to another illustrativeembodiment of the invention.

FIG. 5 is a view of the sling of FIG. 3, including a hydrogel coatingaccording to an illustrative embodiment of the invention.

FIG. 6A is an exemplary end view of a sling according to anotherillustrative embodiment of the invention.

FIG. 6B is a view of the illustrative surgical sling of FIG. 6A.

FIG. 6C is an end view showing an alternative to the illustrativeembodiment of FIG. 6A.

FIG. 6D is an end view of a sling employing channels along both itsfirst and second sides according to an alternative illustrativeembodiment of the invention.

FIG. 6E is an end view of the illustrative sling of FIG. 5A, furtherdepicting well-organized collagenous tissue growth.

FIG. 7 is a view of a sling according to another alternativeillustrative embodiment of the invention.

FIGS. 8A-8C depict one illustrative method for implanting a slingaccording to the invention in the body of a patient.

ILLUSTRATIVE DESCRIPTION

In general, the invention pertains to surgical slings, and relatedmethods for implanting the surgical slings at an anatomical site in thebody of a patient. According to one feature, the surgical slings andrelated methods of the invention promote beneficial tissue growth in theregion of the implanted sling. According to one illustrative embodiment,the tissue is well organized collagenous tissue, such as scar tissue.The phrase “well organized” is intended to mean that the collagenoustissue growth is not completely random, but instead is in some fashioncaused to have some observable organization, direction and/or structure.This organization or well-organized tissue may be either microscopic,such as the arrangement of collagen fibers, or macroscopic, such as acollection of smaller tissues formed into an organized bundle, or acombination of both micro-and macroscopic organization, direction,and/or structures.

The surgical slings of the invention, in various illustrativeembodiments, enable a medical operator to control or affect collagenoustissue properties, such as the size, shape, mass, and/or density of thetissue. The formation of collagenous tissue is the natural response ofthe host body toward any foreign material, such as the surgical sling.As described in further detail below, according some features of theinvention, by selecting properties, such as, the size, shape, textureand/or surface patterning of the sling, the medical operator can controlor affect aspects of collagenous tissue formation. As also describedbelow in further detail, according to other features of the invention,by selecting properties, such as the agent employed, agentconcentration, and/or mode of associating the agent with the sling(e.g., chemically bonding the agent to a subset of the sling fibers,applying the agent as a coating to a subset of the sling fibers,absorbing the agent into sling fibers, blending the agent with thepolymer used to form the sling fibers, impregnate the fibers with theagent and/or applying the agent to openings defined by the fibers in thesling.), the medical operator can further control or affect aspects ofcollagenous tissue formation.

It should be noted that although surgical slings for treating urinaryincontinence are described in the illustrative embodiments, theinvention may be employed, generally, with any suitable medical implant,specifically, with any surgical sling. For example, the sling may be amesh.

According to various illustrative configurations, the surgical sling maybe, for example, in the range of about 5 cm to about 50 cm in length,and about 0.5 cm to about 3 cm wide, though larger or smaller slings maybe employed to suit the size of the patient and/or the application. Thethickness of the surgical sling may be uniform over the entire sling, orthe thickness may vary at one or more different locations. According tovarious illustrative embodiments, the thickness of the surgical slingranges from about 0.01 cm to about 0.2 cm, and in one embodiment isabout 0.08 cm.

The surgical sling of the invention may have any suitable size or shapeconfiguration and may include any complimentary features. By way ofexample, the surgical sling may be rectangular or substantiallyrectangular, trapezoidal, hexagonal, octagonal or elliptical in shape,as may be suitable for its intended location at a particular anatomicalsite. The sling may also have a forked configuration at one or bothends. In some illustrative embodiments, the edges of the sling may belinear in nature (i.e., not tanged) or may have V-shaped projections orbe frayed (i.e., tanged) at the edge. In certain illustrativeembodiments, the surgical sling may have apertures, of any suitableshape and size, for example, round, square, diamond-shaped, ortriangular. In other illustrative embodiments, at least one of the sidesof the surgical sling is textured. The textured or irregular surfaceacts to enhance tissue growth into the sling and also aids instabilization of the sling in the tissue through frictional forces.Without limitation, examples of various sling configurations that may bewith illustrative embodiments of the invention are disclosed in U.S.Ser. No. 10/092,872, entitled “Medical slings,” U.S. Ser. No.10/640,838, entitled “Medical implant,” U.S. Ser. No. 10/641,170,entitled “Medical slings,” and U.S. Ser. No. 10/641,192, entitled“Medical slings,” the entire contents of all of which are incorporatedherein by reference.

According to another illustrative embodiment, the surgical sling of theinvention includes a tensioning mechanism for limiting thestretchability of the surgical sling, aiding in the application of eventension along the length of the sling, and aiding in preventing thesurgical sling from becoming misshapen. Such tensioning mechanism may beembedded in the sling material and/or may be made from resorbable ornon-resorbable suture material. The tensioning device may besubstantially linear or coiled. Examples of resorbable suture materialsinclude, without limitation, polylactic acid (PLA), polyglycolic acid(PGA), and poly-L-lactic acid (PLLA). Examples of non-resorbable suturematerials include, without limitation, polypropylene (PP) andpolybutester. Without limitation, examples of tensioning mechanisms thatmay be employed with illustrative embodiments of the invention aredisclosed in U.S. Pat. No. 6,666,817, entitled “Expandable surgicalimplants and methods of using them,” U.S. Pat. No. 6,669,706, entitled“Thin soft tissue surgical support mesh,” U.S. Pat. No. 6,375,662,entitled “Thin soft tissue surgical support mesh,” U.S. Pat. No.6,042,592, entitled “Thin soft tissue surgical support mesh,” the entirecontents of all of which are incorporated herein by reference.

According to other illustrative embodiments, the surgical sling of theinvention may be employed as part of a sling assembly, including, forexample, a sleeve for enclosing at least a portion of the surgicalsling, and terminating in any suitable configuration or structure suchas loops, apertures, male or female connectors, guide tubes, and thelike. Additionally, the surgical sling of the invention may be employedwith any suitable delivery system. Such delivery systems include, forexample, those delivery systems configured for supra-pubic, pre-pubic,transvaginal, and/or transobturator procedures. Without limitation,examples of sling assemblies, delivery devices and implantationapproaches that may employ illustrative embodiments of the invention aredisclosed in U.S. Ser. No. 10/015,114, entitled “Devices for minimallyinvasive pelvic surgery,” U.S. Ser. No. 10/774,826, entitled “Devicesfor minimally invasive pelvic surgery,” U.S. Ser. No. 10/093,398,entitled “System for implanting an implant and method thereof,” U.S.Ser. No. 10/093,498, entitled “System for implanting an implant andmethod thereof,” U.S. Ser. No. 10/093,371, entitled “System forimplanting an implant and method thereof,” U.S. Ser. No. 10/093,424,entitled “System for implanting an implant and method thereof,” U.S.Ser. No. 10/093,450, entitled “System for implanting an implant andmethod thereof,” U.S. Ser. No. 10/094,352, entitled “System forimplanting an implant and method thereof,” U.S. Ser. No. 10/631,364,entitled “Bioabsorbable casing for surgical sling assembly,” U.S. Ser.No. 10/641,376, entitled “Spacer for sling delivery system,” U.S. Ser.No. 10/641,487, entitled “Systems, methods and devices relating todelivery of medical implants,” U.S. Ser. No. 10/642,395, entitled“Systems, methods and devices relating to delivery of medical implants,”U.S. Ser. No. 10/642,397, entitled “Systems, methods and devicesrelating to delivery of medical implants,” U.S. Ser. No. 10/832,653,entitled “Systems and methods for sling delivery and placement,” U.S.Provisional Application No. 60/569,300, entitled “Systems and methodsfor delivering a medical implant to an anatomical location in apatient,” and U.S. Provisional Application No. 60/508,600 entitled“Systems and methods for delivering a medical implant to an anatomicallocation in a patient,” the entire contents of all of which areincorporated herein by reference.

Turning to the illustrative drawings, FIG. 1 depicts a view showing afirst side 124 of a surgical sling 100 according to an illustrativeembodiment of the invention. The sling 100 is generally rectangular inshape and flat, or sheet-like, with a first side 124, which is seen inthis view, and a second side 126, which cannot be seen in this view. Asshown, the sling 100 is manufactured from a plurality of fibers 104, andincludes at least one agent 108. According to the illustrativeembodiment of FIG. 1, the agent 108 includes a tissue growth promotingagent, but any suitable agent may be employed. The fibers used to weavethe sling sheet may extend in at least two directions, i.e., X- andY-directions. The fibers extending in the different directions may bedifferent in term of chemical composition, the agent loaded, physicaldimensions, such as diameter, and surface properties to suit the needsof promoting organized tissue formation, such as guide the collagenoustissue growth, particularly scar tissue, in one preferred direction.

The fibers 104 of the sling 100 are made of a biocompatible material andmay be, for example, knitted or weaved to form the sling 100. As usedherein, the term “biocompatible” refers to a material that issubstantially non-toxic and that does not induce a significantly adverseeffect on the patient's health. According to the illustrativeembodiment, at least a portion of the sling 100 is biodegradeable. Forexample, in one illustrative embodiment, the fibers 104 arebiodegradable. However, this need not be the case. By way of example, inother illustrative embodiments, only a section of the surgical sling100, such as, for example, a mid-length section, is biodegradable. Forexample, in one embodiment, only a corresponding mid-length section ofthe fibers 104 are biodegradable. In some illustrative embodiments, thefibers 104 in the other sections of the surgical sling 100 are made of anon-bioabsorbable material. In some such embodiments, the biodegradablemid-length section has a length of about 1 mm to about 25 mm, about 5 mmto about 15 mm, or, most preferably, about 5 mm to about 10 mm.Exemplary biodegradable materials, in addition the listed above, thatmay be used in accordance with the invention include, but are notlimited to, human dermis and decellularized animal tissue. Human tissuesmay be derived, for example, from human cadaveric or engineered humantissue. Animal tissues may be derived, for example, from porcine, ovine,bovine, and equine tissue sources. Additionally, exemplary biodegradablepolymers that may be used in accordance with the invention include, butare not limited to, polylactic acid, polyglycolic acid and copolymersand mixtures thereof, such as poly(L-lactide) (PLLA), poly(D,L-lactide)(PLA), polyglycolic acid [polyglycolide (PGA)],poly(L-lactide-co-D,L-lactide) (PLLA/PLA), poly(L-lactide-co-glycolide)(PLLA/PGA), poly(D,L-lactide-co-glycolide) (PLA/PGA),poly(glycolide-co-trimethylene carbonate) (PGA/PTMC),poly(D,L-lactide-co-caprolactone) (PLA/PCL), andpoly(glycolide-co-caprolactone) (PGA/PCL); polyethylene oxide (PEO);polydioxanone (PDS); polypropylene fumarate; polydepsipeptides,poly(ethyl glutamate-co-glutamic acid),poly(tert-butyloxy-carbonylmethyl glutamate); polycaprolactone (PCL),poly(hydroxy butyrate), polycaprolactone co-butylacrylate,polyhydroxybutyrate (PHBT) and copolymers of polyhydroxybutyrate;polyphosphazenes, poly(phosphate ester); maleic anhydride copolymers,polyiminocarbonates, poly[(97.5% dimethyl-trimethylenecarbonate)-co-(2.5% trimethylene carbonate)], cyanoacrylate,hydroxypropylmethylcellulose; polysaccharides, such as hyaluronic acid,chitosan and regenerate cellulose; poly(amino acid) and proteins, suchas gelatin and collagen; and mixtures and copolymers thereof. The slingmaterial may also be made of a combination of mammalian tissue andsynthetic material(s).

One illustrative agent 108 used in accordance with the inventionpromotes, when applied to the patient's tissues in a pharmaceuticallyacceptable amount, well-organized collagenous tissue growth, such asscar tissue growth, preferably, in large quantities. According to onefeature, the agent 108 may or may not block or delay thebiodegradability of the sling 100. This may be controlled by selectingdifferent methods to load the agent onto the sling fibers. As mentionedabove, the agent 108 may include a growth factor. The growth factor mayinclude natural and/or recombinant proteins to stimulate a tissueresponse so that collagenous tissue such as scar tissue growth isenhanced. Exemplary growth factors that may be used in accordance withthe invention to promote such tissue growth include, but are not limitedto, platelet-derived growth factor (PDGF), fibroblast growth factor(FGF), transforming growth factor-beta (TGF-beta), vascular endotheliumgrowth factor (VEGF), Activin/TGF and sex steroid, bone marrow growthfactor, growth hormone, Insulin-like growth factor 1, and combinationsthereof. The agent may also be a hormone, including but not limited toestrogen, steroid hormones, and other hormones to promote growth ofappropriate collagenous tissue such as scar tissue. The agent may alsoinclude stem cells or other suitable cells derived from the hostpatient. These cells may be fibroblast, myoblast, or other progenitorcells to mature into appropriate tissues.

In various illustrative embodiment, the agent 108 may include one ormore therapeutic agents. The therapeutic agents may be, for example,anti-inflammatory agents, including steroidal and non-steroidalanti-inflammatory agents, analgesic agents, including narcotic andnon-narcotic analgesics, local anesthetic agents, antispasmodic agents,growth factors, gene-based therapeutic agents, and combinations thereof.

Exemplary steroidal anti-inflammatory therapeutic agents(glucocorticoids) include, but are not limited to,21-acetoxyprefnenolone, aalclometasone, algestone, amicinonide,beclomethasone, betamethasone, budesonide, chloroprednisone, clobetasol,clobetasone, clocortolone, cloprednol, corticosterone, cortisone,cortivazol, deflazacort, desonide, desoximetasone, dexamethasone,diflorasone, diflucortolone, difluprednate, enoxolone, fluazacort,flucloronide, flumehtasone, flunisolide, fluocinolone acetonide,fluocinonide, fluocortin butyl, fluocortolone, fluorometholone,fluperolone acetate, fluprednidene acetate, fluprednisolone,flurandrenolide, fluticasone propionate, formocortal, halcinonide,halobetasol priopionate, halometasone, halopredone acetate,hydrocortamate, hydrocortisone, loteprednol etabonate, mazipredone,medrysone, meprednisone, methyolprednisolone, mometasone furoate,paramethasone, prednicarbate, prednisolone, prednisolone25-diethylaminoacetate, prednisone sodium phosphate, prednisone,prednival, prednylidene, rimexolone, tixocortal, triamcinolone,triamcinolone acetonide, triamcinolone benetonide, triamcinolonehexacetonide, and pharmaceutically acceptable salts thereof.

Exemplary non-steroidal anti-inflammatory therapeutic agents include,but are not limited to, aminoarylcarboxylic acid derivatives such asenfenamic acid, etofenamate, flufenamic acid, isonixin, meclofenamicacid, mefanamic acid, niflumic acid, talniflumate, terofenamate andtolfenamic acid; arylacetic acid derivatives such as acemetacin,alclofenac, amfenac, bufexamac, cimnetacin, clopirac, diclofenac sodium,etodolac, felbinac, fenclofenac, fenclorac, fenclozic acid, fentiazac,glucametacin, ibufenac, indomethacin, isofezolac, isoxepac, lonazolac,metiazinic acid, oxametacine, proglumetacin, sulindac, tiaramide,tolmetin and zomepirac; arylbutyric acid derivatives such as burnadizon,butibufen, fenbufen and xenbucin; arylcarboxylic acids such as clidanac,ketorolac and tinoridine; arylpropionic acid derivatives such asalminoprofen, benoxaprofen, bucloxic acid; carprofen, fenoprofen,flunoxaprofen, flurbiprofen, ibuprofen, ibuproxam, indoprofen,ketoprofen, loxoprofen, miroprofen, naproxen, oxaprozin, piketoprofen,pirprofen, pranoprofen, protizinic acid, suprofen and tiaprofenic acid;pyrazoles such as difenamizole and epirizole; pyrazolones such asapazone, benzpiperylon, feprazone, mofebutazone, morazone,oxyphenbutazone, phenybutazone, pipebuzone, propyphenazone,ramifenazone, suxibuzone and thiazolinobutazone; salicylic acidderivatives such as acetaminosalol, aspirin, benorylate, bromosaligenin,calcium acetylsalicylate, diflunisal, etersalate, fendosal, gentisicacid, glycol salicylate, imidazole salicylate, lysine acetylsalicylate,mesalamine, morpholine salicylate, 1-naphthyl salicylate, olsalazine,parsalmide, phenyl acetylsalicylate, phenyl salicylate, salacetamide,salicylamine o-acetic acid, salicylsulfuric acid, salsalate andsulfasalazine; thiazinecarboxamides such as droxicam, isoxicam,piroxicam and tenoxicam; others such as ε-acetamidocaproic acid,s-adenosylmethionine, 3-amino-4-hydroxybutyric acid, amixetrine,bendazac, benzydamine, bucolome, difenpiramide, ditazol, emorfazone,guaiazulene, nabumetone, nimesulide, orgotein, oxaceprol, paranyline,perisoxal, pifoxime, proquazone, proxazole and tenidap; andpharmaceutically acceptable salts thereof.

Exemplary narcotic analgesic therapeutic agents include, but are notlimited to, alfentanil, allylprodine, alphaprodine, anileridine,benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene,codeine, codeine methyl bromide, codeine phosphate, codeine sulfate,desomorphine, dextromoramide, dezocine, diampromide, dihydrocodeine,dihydrocodeinone enol acetate, dihydromorphine, dimenoxadol,dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone,eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine,etonitazene, fentanyl, hydrocodone, hydromorphone, hydroxypethidine,isomethadone, ketobemidone, levorphanol, lofentanil, meperidine,meptazinol, metazocine, methadone hydrochloride, metopon, morphine,myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol,normethadone, normorphine, norpipanone, opium, oxycodone, oxymorphone,papaveretum, pentazocine, phenadoxone, phenazocine, pheoperidine,piminodine, piritramide, proheptazine, promedol, properidine, propiram,propoxyphene, rumifentanil, sufentanil, tilidine, and pharmaceuticallyacceptable salts thereof.

Exemplary non-narcotic analgesic agents that maybe combined with thesling 100 include, but are not limited to, aceclofenac, acetaminophen,acetaminosalol, acetanilide, acetylsalicylsalicylic acid, alclofenac,alminoprofen, aloxiprin, aluminum bis(acetylsalicylate),aminochlorthenoxazin, 2-amino-4-picoline, aminopropylon, aminopyrine,ammonium salicylate, amtolmetin guacil, antipyrine, antipyrinesalicylate, antrafenine, apazone, aspirin, benorylate, benoxaprofen,benzpiperylon, benzydamine, bermoprofen, brofenac, p-bromoacetanilide,5-bromosalicylic acid acetate, bucetin, bufexamac, burnadizon,butacetin, calcium acetylsalicylate, carbamazepine, carbiphene,carsalam, chloralantipyrine, chlorthenoxazin(e), choline salicylate,cinchophen, ciramadol, clometacin, cropropamide, crotethamide,dexoxadrol, difenamizole, diflunisal, dihydroxyaluminumacetylsalicylate, dipyrocetyl, dipyrone, emorfazone, enfenamic acid,epirizole, etersalate, ethenzamide, ethoxazene, etodolac, felbinac,fenoprofen, floctafenine, flufenamic acid, fluoresone, flupirtine,fluproquazone, flurbiprofen, fosfosal, gentisic acid, glafenine,ibufenac, imidazole salicylate, indomethacin, indoprofen, isofezolac,isoladol, isonixin, ketoprofen, ketorolac, p-lactophenetide, lefetamine,loxoprofen, lysine acetylsalicylate, magnesium acetylsalicylate,methotrimeprazine, metofoline, miroprofen, morazone, morpholinesalicylate, naproxen, nefopam, nifenazone, 5′ nitro-2′propoxyacetanilide, parsalmide, perisoxal, phenacetin, phenazopyridinehydrochloride, phenocoll, phenopyrazone, phenyl acetylsalicylate, phenylsalicylate, phenyramidol, pipebuzone, piperylone, prodilidine,propacetamol, propyphenazone, proxazole, quinine salicylate,ramifenazone, rimazolium metilsulfate, salacetamide, salicin,salicylamide, salicylamide o-acetic acid, salicylsulfuric acid,salsalte, salverine, simetride, sodium salicylate, sulfamipyrine,suprofen, talniflumate, tenoxicam, terofenamate, tetradrine, tinoridine,tolfenamic acid, tolpronine, tramadol, viminol, xenbucin, zomepirac, andpharmaceutically acceptable salts thereof.

Exemplary local anesthetic therapeutic agents include, but are notlimited to, ambucaine, amolanone, amylocalne hydrochloride, benoxinate,benzocaine, betoxycaine, biphenamine, bupivacaine, butacaine, butaben,butanilicaine, butethamine, butoxycaine, carticaine, chloroprocainehydrochloride, cocaethylene, cocaine, cyclomethycaine, dibucainehydrochloride, dimethisoquin, dimethocaine, diperadon hydrochloride,dyclonine, ecgonidine, ecgonine, ethyl chloride, beta-eucaine, euprocin,fenalcomine, fomocaine, hexylcaine hydrochloride, hydroxytetracaine,isobutyl p-aminobenzoate, leucinocaine mesylate, levoxadrol, lidocaine,mepivacaine, meprylcaine, metabutoxycaine, methyl chloride, myrtecaine,naepaine, octacaine, orthocaine, oxethazaine, parethoxycaine, phenacainehydrochloride, phenol, piperocaine, piridocaine, polidocanol, pramoxine,prilocalne, procaine, propanocaine, proparacaine, propipocaine,propoxycaine hydrochloride, pseudococaine, pyrrocaine, ropavacaine,salicyl alcohol, tetracaine hydrochloride, tolycaine, trimecaine,zolamine, and pharmaceutically acceptable salts thereof.

Exemplary antispasmodic therapeutic agents include, but are not limitedto, alibendol, ambucetamide, aminopromazine, apoatropine, bevoniummethyl sulfate, bietamiverine, butaverine, butropium bromide,n-butylscopolammonium bromide, caroverine, cimetropium bromide,cinnamedrine, clebopride, coniine hydrobromide, coniine hydrochloride,cyclonium iodide, difemerine, diisopromine, dioxaphetyl butyrate,diponium bromide, drofenine, emepronium bromide, ethaverine, feclemine,fenalamide, fenoverine, fenpiprane, fenpiverinium bromide, fentoniumbromide, flavoxate, flopropione, gluconic acid, guaiactamine,hydramitrazine, hymecromone, leiopyrrole, mebeverine, moxaverine,nafiverine, octamylamine, octaverine, oxybutynin chloride,pentapiperide, phenamacide hydrochloride, phloroglucinol, pinaveriumbromide, piperilate, pipoxolan hydrochloride, pramiverin, prifiniumbromide, properidine, propivane, propyromazine, prozapine, racefemine,rociverine, spasmolytol, stilonium iodide, sultroponium, tiemoniumiodide, tiquizium bromide, tiropramide, trepibutone, tricromyl,trifolium, trimebutine, n,n-ltrimethyl-3,3-diphenyl-propylamine,tropenzile, trospium chloride, xenytropium bromide, and pharmaceuticallyacceptable salts thereof.

Two particular therapeutic agents employed in various illustrativeembodiments of the invention are: (a) ketorolac and pharmaceuticallyacceptable salts thereof (e.g., the tromethamine salt thereof, soldunder the commercial trade name Toradol®) and (b)4-diethylamino-2-butynylphenylcyclohexylglycolate and pharmaceuticallyacceptable salts thereof (e.g.,4-diethylamino-2-butynylphenylcyclohexylglycolate hydrochloride, alsoknown as oxybutynin chloride, sold under the commercial trade nameDitropan®).

The agent 108, as described below, maybe associated with the sling 100in a variety of manners. For example, referring again to FIG. 1, theagent 108 may be chemically or physically attached to the surface of oneor more of the biocompatible fibers 104. In one illustrative embodiment,the surface of the biocompatible fibers 104 and the agent 108, forexample, in solution, have complementary ionic charges. As such, whenplaced on the fibers 104, the agent 108 ionically bonds to the surfaceof the fibers 104. In another illustrative embodiment, beforeapplication of the agent 108, a coating is applied to the surface of thefibers 104. For example, a hydrophilic or hydrophobic coating is appliedto the surface of the fibers 104. The hydrophilic or hydrophobic coatingabsorbs a hydrophilic or hydrophobic agent 108, respectively, to thesurface of the fibers 104. In yet another embodiment, the hydrophilic orhydrophobic coating and the hydrophilic or hydrophobic agent 108,respectively, are mixed together to form a single coating and thenapplied to the surface of the fibers 104. Alternatively, in anotherillustrative embodiment, the agent 108 is in the form of, for example, apaste or a gel. The agent 108 is itself applied as a coating to thesurface of the fibers 104 and held in place by, for example, friction.In other illustrative embodiments, any suitable methodology forassociating the agent 108 with the fibers 104, such that the agent 108can leach to tissue in the region of the implanted sling 100, may beemployed.

FIG. 2 depicts a surgical sling 100 according to another illustrativeembodiment of the invention. As shown, rather than being attached to thesurface of the biocompatible fibers 104, as in FIG. 1, the agent 108 isintegrally combined with the fibers 104. This integral combination maybe achieved in a variety of ways. For example, in one illustrativeembodiment, the agent 108 is initially blended with a polymer. The agent108/polymer blend is then used to fabricate the fibers 104. The fibers104, fabricated from the agent 108/polymer blend, are knitted or weaved,for example, to construct the sling 100. In another illustrativeembodiment, the agent 108 loaded fiber is knitted or weaved into thefibers extending in one direction, for example, the X direction, topromoted guided/oriented tissue growth/attachment. In one illustrativeembodiment, the agent 108 is impregnated into the finished sling ormesh. In another illustrative embodiment, the fibers 104 are made of awettable material. The agent 108, for example, in solution, is thenapplied to and absorbed into the fibers 104.

FIG. 3 depicts another illustrative embodiment of the surgical sling100. In this example, the sling may be made of two or more types offibers knitted or woven together to construct the sling 100. The fibers104 and the fibers 105 may be made from different materials and maypossess different characteristics from each other. The fibers 104 extendin direction X relative to the orientation of the surgical sling 100 andthe fibers 105 extend in direction Y, different from the direction ofthe fibers 104, relative to the orientation of the surgical sling 100.In one illustrative embodiment, the fibers 104 may be fabricated with anagent 108. In another embodiment, the fibers 105 are fabricated with anagent 108. In another embodiment, the differences of the chemical andphysical characteristics of the fibers 104 and 105, without additionalagent, guide the formation of well-organized collagenous tissue such asscar tissue. Alternatively, in one embodiment, the fibers 104 havesurface features that promote the growth of well-organized collagenoustissue such as scar tissue. In a yet another embodiment, these surfacestructures are combined with the presence of the agent 108.

In another illustrative embodiment of the surgical sling 100, asdepicted in FIG. 4, the fibers 104 of the surgical sling 100 define oneor more openings 116 in the sling 100. The openings 116 may assume anyshape or size relative to the sling 100. As illustrated in FIG. 5, ahydrogel coating 120, which contains the agent 108, and which,preferably, has a high enough viscosity to maintain the agent 108 in theopenings 116, is applied to the sling 100 to fill the openings 116.

Referring again to FIG. 4, in an alternative illustrative embodiment, anabsorbable foam material (not shown) is disposed into the openings 116.Alternatively, the foam material may be embedded into the sling 100 soas to be present in the openings 116. The foam material is then, forexample, thermally bonded to the sling 100. The agent 108, for example,in solution, is subsequently applied to and absorbed by the foammaterial. The foam material may be manufactured from, for example,polyvinyl acetate (PVA), polyurethane, silicone, polyester,polyethylene, gelatin, hyaluronic acid, chitosan, regenerate cellulose,or other suitable materials.

According to another illustrative embodiment, the invention employssurface patterning on the surgical sling 100, alone or in combinationwith the agent 108, to promote well-organized collagenous tissue growth.Referring to FIGS. 6A-6C, in one illustrative embodiment, the first side124 of the sling 100 includes one or more longitudinal channels 128. Thechannels 128 may be formed by longitudinally extending raisedprojections 129 on the first side 124, as illustrated in FIG. 6A.Alternatively, the channels 128 may be formed into the first side 124,as illustrated in FIG. 6C. As shown in FIG. 6B which is a view showingthe first side 124, the channels 128 extend along the entire length ofthe surgical sing 100, from a first end 132 to a second end 136.However, this need not be the case. In alternative embodiments, thechannels 128 extend an intermediate distance between the ends 132 and136.

As shown in FIG. 6D, in other illustrative embodiments, the channels 128may extend axially along both the first 124 and second 126 sides of thesurgical sling 100. As discussed in further detail below with respect toFIGS. 8A-8C, and as indicated in FIG. 6E, as collagenous tissue growthoccurs, the channels or surface pattern 128, engage the fibroblast cellsand/or collagenous tissue 152 and improve cell/tissue attachment on tothe sling and therefore guide its growth, such that the collagenoustissue 152, such as scar tissue, grows in the channels 128 as awell-organized, as opposed to a randomized, tissue 152.

Referring now to FIG. 7, the surgical sling 100 may include one or morethrough holes/appertures 140. In the illustrative embodiment of FIG. 7,the through holes 140 are formed as perforations that pass from thefirst side 124 through to the second side 126 of the surgical sling 100.Following stimulation of the patient's periurethral tissues by the agent108, through holes 140 engage the resulting collagenous tissue 152. Thecollagenous tissue 152 grows in such a manner as to pass in and out ofthe through holes 140 and incorporate the surgical sling 100. As such,the tissue 152 grows in a well-organized, as opposed to a randomized,manner surrounding the sling and/or sling fibers.

The sides 124 and/or 126 of the surgical sling 100 may, in otherillustrative embodiments, include other patterns or designs to promotefibroblast proliferation, and the well-organized collagenous tissuegrowth. For example, the sides 124 and/or 126 may includetexturing/roughening, such as, without limitation, one or moreprojections, depressions, rises, ridges, valleys, embossing, orcombinations of any thereof. The texture may be formed by employingfibers 104 having various cross-sectional shapes, such as, circular,ovoid, square, rectangular, star, or irregular shapes. The surgicalsling 100 may also includes portions having a varying thickness and/orwidth, which may be achieved, for example, by employing fibers 104having varying diameters and/or by changing knit and/or weave density.Other patterns and designs may be formed on the sides 124 and 126 of thesurgical sling 100 by any suitable approach.

In other illustrative embodiments, the invention provides methods fortreating urinary incontinence. Generally, referring to FIG. 8A, thesurgical sling 100 is implanted in a patient's periurethral tissues 144and positioned adjacent the patient's urethra 148. Initially, thesurgical sling 100 provides physical support to the patient's urethra148. The sling 100 releases the agent 108 into tissue near theimplantation site to stimulate collagenous tissue growth. According toone feature, the structure of the surgical sling 100 encourageswell-organized collagenous tissue growth. Referring now to FIG. 8B,after a pre-determined period of time, such as, for example, about two(2) to about eight (8) weeks, the newly formed tissue 152 begins tosupport the patient's urethra 148. As illustrated in FIG. 8C, in oneillustrative embodiment, the sling 100 is biodegradable, and after anadditional pre-determined period of time, such as, for example, aboutthree (3) to about six (6) months, the sling 100 is completelybiodegraded.

A natural tissue based sling 156, formed from the collagenous tissue152, is left behind in the patient's periurethral tissues 144, adjacentthe urethra 148. The natural tissue based sling 156 provides therequisite support to assist in maintaining continence. The naturaltissue based sling 156 may be capable of adjusting itself to the anatomyof the patient's body changes without causing injury to the patient,such as increase in necessary length as the body gains additionalweight.

Variations, modifications, and other implementations of what isdescribed may be employed without departing from the spirit and thescope of the invention.

1. A surgical implant comprising a surgical sling for implantation at ananatomical site in a body of a patient, and an agent, associated withthe surgical sling, and including a pharmaceutical for promotingcollagenous tissue growth near the anatomical site.
 2. The surgicalimplant of claim 1, wherein the agent includes a therapeutic agent. 3.The surgical implant of claim 1, wherein the agent includes a growthfactor.
 4. The surgical implant of claim 1, wherein the agent includes astem cell.
 5. The surgical implant of claim 1, wherein the agentincludes a fibroblast.
 6. The surgical implant of claim 1, wherein theagent includes a myoblast.
 7. The surgical implant of claim 1, whereinthe agent includes at least one of an analgesic agent, anesthetic agentand an antispasmodic agent.
 8. The surgical implant of claim 1, whereinthe surgical sling includes surface features for promoting organizedcollagenous tissue growth.
 9. The surgical implant of claim 8, whereinthe surgical sling has first and second sides and the surface featuresare located on at least one of the first and second sides.
 10. Thesurgical implant of claim 8, wherein the surgical sling has first andsecond sides and the surface features include through aperturesextending between the first and second sides.
 11. The surgical implantof claim 8, wherein the surgical sling has first and second sides, bothincluding the surface features.
 12. The surgical implant of claim 8,wherein the surface features include channels extending axially along atleast a portion of a side of the surgical sling.
 13. The surgicalimplant of claim 12, wherein the channels extend along substantially anentire length of the surgical sling.
 14. The surgical implant of claim12, wherein the channels are formed into the side of the surgical sling.15. The surgical implant of claim 12, wherein the channels are definedby projections extending axially along the side of the surgical sling.16. The surgical implant of claim 1, wherein the surgical sling has avarying thickness for promoting collagenous tissue growth.
 17. Thesurgical implant of claim 16, wherein the surgical sling includes fibershaving varying diameters for realizing the varying thickness.
 18. Thesurgical implant of claim 1, wherein the surgical sling as a varyingwidth for promoting collagenous tissue growth.
 19. The surgical implantof claim 18, wherein the surgical sling includes fibers having diametersthat vary along their length for realizing the varying width.
 20. Thesurgical implant of claim 1, wherein the surgical sling includes aplurality of elongated fibers and the agent is chemically bonded to asubset of the elongated fibers.
 21. The surgical implant of claim 1,wherein the surgical sling includes a plurality of elongated fibers andthe agent is applied as a coating on the elongated fibers.
 22. Thesurgical implant of claim 1, wherein the surgical sling includes aplurality of elongated fibers and the agent is absorbed within theelongated fibers.
 23. The surgical implant of claim 1, wherein thesurgical sling includes a polymer and the agent is blended with thepolymer prior to forming the surgical sling.
 24. The surgical implant ofclaim 1, wherein the surgical sling is formed from a synthetic material.25. The surgical implant of claim 1, wherein the surgical sling includesat least one of human dermis, decellularized animal tissue, hyaluronicacid, chitosan, regenerate cellulose, gelatin, collagen and combinationsthereof.
 26. The surgical implant of claim 1, wherein the surgical slingis substantially biodegradable.
 27. The surgical implant of claim 1,wherein the surgical sling is substantially biodegradable in a region,the region being less than an entirety of the surgical sling.
 28. Thesurgical implant of claim 27, wherein the surgical sling employs fibershaving biodegradable regions to realize the biodegradable region of thesurgical sling.
 29. A surgical implant comprising a surgical sling forimplantation at an anatomical site in a body of a patient and an agent,associated with the surgical sling, wherein the agent comprises apharmaceutical for promoting tissue growth near the anatomical site. 30.The surgical implant of claim 29, wherein the surgical sling comprisesat least two types of fibers, the first type of fibers extending in afirst direction and the second type of fibers extending in a seconddirection.
 31. The surgical implant of claim 30, wherein the first typeof fibers comprises surface features for promoting well-organized tissuegrowth.
 32. The surgical implant of claim 30, wherein the agent isassociated with first type of fibers.